Emily L. Postma

Localization of nonpalpable breast lesions

The introduction of mammography screening and improvements in diagnostic tools resulted in a major increase of breast cancers detectable as small, nonpalpable lesions suitable for breast-conserving treatment. Accurate preoperative localization of these cancers is a necessity. Several methods are available for localization, of which wire-guided localization is considered the current gold standard. Promising techniques are radio-guided occult lesion localization, radioactive seed localization and ultrasound-guided surgery. In this article, an overview of the various localization techniques is provided, describing advantages, shortcomings and effectiveness.

MRI‐guided ablation of breast cancer: Where do we stand today?

The treatment of patients with localized breast cancer has changed considerably over the past few decades. The next challenge is to use image‐guided minimally invasive tumor ablation techniques. The fact that MRI is the most accurate imaging modality for visualization and delineation of breast tumor margins in three dimensions and provides MRI‐based temperature mapping, makes it particularly applicable for monitoring during minimally invasive ablation techniques. The overall result of the studies performed on MRI‐guided minimally invasive tumor ablation studies are varying, with reported total tumor ablation rates ranging between 20% and 100%. Strict selection of patients, consensus on the treatment zone margin and optimization of MR‐imaging, should make MRI‐guided breast cancer tumor ablation a useful tool in clinical practice. J. Magn. Reson. Imaging 2011;.

Contemporary Locoregional Recurrence Rates in Young Patients With Early-Stage Breast Cancer

PURPOSE The aim of this study was to evaluate contemporary rates of local recurrence (LR) and regional recurrence (RR) in young patients with breast cancer in relation to tumor biology as expressed by biomarker subtypes. PATIENTS AND METHODS Women < 35 years of age who underwent surgery for primary unilateral invasive breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. Patients were categorized according to biomarker subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year risks of developing LR and regional lymph node recurrence were estimated by using Kaplan-Meier statistics. RESULTS A total of 1,000 patients were identified, of whom 59% had a known subtype: 39% HR-positive/HER2-negative; 17% HR-positive/HER2-positive; 10% HR-negative/HER2-positive; and 34% HR-negative/HER2-negative (triple negative). Overall 5-year LR and RR rates were 3.5% and 3.7%, respectively. A decreasing trend for both rates was observed over time and was accompanied by a significant decrease in the risk of distant metastases (DM). LR occurred in 4.2%, RR in 6.1%, and DM in 17.8% of patients in 2003, and in 3.2%, 4.4%, and 10.0%, respectively, in 2008. LR and RR rates varied with biomarker subtype. These differences were borderline significant when analyzed for the entire study period (P = .056 and P = .014, respectively) and leveled off after the introduction of trastuzumab after 2005 (P = .24 and P = .42, respectively). Patients with lymph node metastases at the time of diagnosis had an increased risk of RR. The type of surgery performed-breast-conserving or mastectomy-did not influence rates of LR and RR. CONCLUSION Overall, the rates of LR and RR in young patients with early-stage breast cancer were relatively low and varied by biomarker subtype.

Radiofrequency ablation of small breast tumours: evaluation of a novel bipolar cool-tip application.

BACKGROUND Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, burns are a frequent complication. The safety and efficacy of a new technique with a bipolar RFA electrode was evaluated. METHODS Dosimetry was assessed ex vivo in bovine mammary tissue, applying power settings of 5-15 W with 10-20 min exposure and 3.0-12.0 kJ to a 20-mm active length bipolar internally cooled needle-electrode. Subsequently, in 15 women with invasive breast carcinoma ≤2.0 cm diameter ultrasound-guided RFA was performed followed by immediate resection. RESULTS An ablation zone of 2.5 cm was reached in the ex vivo experiments at 15 W at 9.0 kJ administered energy. Histopathology revealed complete cell death in 10 of 13 patients (77%); in 3 patients partial ablation was due to inaccurate probe positioning. In 1 patient a pneumothorax was caused by the probe placement, treated conservatively. No burns occurred. CONCLUSIONS Ultrasound-guided RFA with a bipolar needle-electrode appears to be a safe local treatment technique for invasive breast cancer up to 2 cm. Ways to improve placement of the probe and direct monitoring of the ablation-effect should be the aim of further research.

Prediction of positive resection margins in patients with non-palpable breast cancer

BACKGROUND In patients undergoing breast conserving surgery for non-palpable breast cancer, obtaining tumour free resection margins is important to prevent reexcision and local recurrence. We developed a model to predict positive resection margins in patients undergoing breast conserving surgery for non-palpable invasive breast cancer. METHODS A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery in five hospitals in the Netherlands. A prediction model for positive resection margins was developed using multivariate logistic regression. Calibration and discrimination of the model were assessed and the model was internally validated by bootstrapping. RESULTS Positive resection margins were present in 69/576 (12%) patients. Factors independently associated with positive resection margins included mammographic microcalcifications (OR 2.14, 1.22-3.77), tumour size (OR 1.75, 1.20-2.56), presence of DCIS (OR 2.61, 1.41-4.82), Bloom and Richardson grade 2/3 (OR 1.82, 1.05-3.14), and caudal location of the lesion (OR 2.4, 1.35-4.27). The model was well calibrated and moderately able to discriminate between patients with positive versus negative resection margins (AUC 0.70, 95% CI, 0.63-0.77, and 0.69 after internal validation). CONCLUSION The presented prediction model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning and preoperative patient counselling.

Invasive ductolobular carcinoma of the breast: spectrum of mammographic, ultrasound and magnetic resonance imaging findings correlated with proportion of the lobular component

PurposeThe aim of this study was to describe the imaging features of patients with invasive ductolobular carcinoma of the breast in comparison with the proportion of the lobular component.Materials and methodsWe retrospectively reviewed mammographic, sonographic and MRI records of 113 patients with proven ductolobular carcinoma diagnosed between January 2008 and October 2012 according to the BI-RADS ® lexicon, and correlated these to the proportion of the lobular component.ResultsAt mammography the most common finding (62.9%) for invasive ductolobular carcinoma was an irregular, spiculated and isodense mass. On ultrasound an irregular and hypoechoic mass, with spiculated margins and posterior acoustic shadowing was observed in 46.8% of cases. Isolated mass and mass associated with non-mass like enhancement (NMLE) were the most common findings by MRI (89.4%). Washout pattern in delayed phase was seen in 61.2% and plateau curve was more frequently observed in patients with larger lobular component. Additional malignant findings (multifocality, multicentricity and contralateral disease) did not correlate significantly with the proportion of the lobular component.ConclusionInvasive ductolobular carcinoma mainly presents as an irregular, spiculated mass, isodense on mammography and hypoechoic with posterior acoustic shadowing. On MRI it is usually seen as an isolated mass or as a dominant mass surrounded by smaller masses or NMLE. Washout is the most ordinary kinetic pattern of these tumors. In general, the imaging characteristics did not vary significantly with the proportion of the lobular component.

High Prevalence of MRI-Detected Contralateral and Ipsilateral Malignant Findings in Patients With Invasive Ductolobular Breast Cancer: Impact on Surgical Management

INTRODUCTION Invasive breast cancer comprises a spectrum of histologic changes with purely lobular and purely ductal cancer on either side and mixed lesions in between. Our aim was to evaluate to what extent preoperative magnetic resonance imaging (MRI) leads to the finding of additional malignancies and the effect on surgical management in the subcategory of women with invasive ductolobular disease. PATIENTS AND METHODS From 2007 to 2012, 109 patients diagnosed with breast cancer containing a lobular component underwent preoperative MRI. The MRI findings were compared with the findings from mammography and ultrasonography. Clinically relevant additional MRI findings were verified histologically. The histologic slides were reviewed, and the percentage of the lobular component was determined. In a multidisciplinary setting, the TNM classification and surgical policy were determined using the conventional imaging findings and as a scenario that included preoperative MRI. RESULTS MRI revealed additional malignant foci in 28 of 109 patients (26%). More extensive disease was seen in 25 patients (23%). The preoperative MRI findings changed the TNM classification in 42% of the patients and altered the surgical policy in 37%. No correlation was found between the lobular component and the probability of detecting additional malignant foci, more extensive disease, or the frequency of a change in TNM classification or surgical policy. According to the final pathology report, the change in surgical policy was justified in 85% of the patients. CONCLUSION In patients with breast cancer presenting with lobular differentiation at biopsy, preoperative MRI can lead to the detection of additional malignancies and clinically relevant changes in surgical policy in a high percentage of patients, irrespective of the lobular component. The use of MRI as a part of the standard workup of such patients deserves consideration.

Discrepancy between routine and expert pathologists' assessment of non-palpable breast cancer and its impact on locoregional and systemic treatment.

Histopathological parameters are essential for deciding on adjuvant treatment following breast cancer surgery. We assessed the impact of inter-observer variability on treatment strategy in patients operated for clinically node negative, non-palpable breast carcinomas. In the context of a multicenter randomised controlled trial, clinical and histological data of 310 patients with clinically node negative non-palpable invasive breast cancer were prospectively collected. Histological assessment of the primary tumour and sentinel nodes was first performed in a routine setting, subsequently central review took place. In case of discordance between local en central assessments, we determined the impact on locoregional and systemic treatment strategy. Discordance between local and central review was observed in 13% of the patients for type (kappa 0.60, 95% CI 0.50-0.71), in 12% for grade (k=0.796, 95% CI 0.73-0.86), in 1% for ER status (k=0.898, 95% CI 0.80-1.0), in 2% for PR status (k=0.940 95% CI 0.89-0.99). Discrepancy in the assessment of the sentinel node(s) was seen in 2% of the patients (k=0.954, 95% CI 0.92-0.98). Applying current Dutch Guidelines, central review would have affected locoregional treatment in 2% (7/310), systemic treatment in 5% (16/310) and both in 1% (2/310) of the patients. For the 9 (3%) patients in whom central review would have led to additional systemic treatment, Adjuvant! predicted 10 years mortality and recurrence rate would have decreased with a median of 4.6% and 15%, respectively. Discordance between routine histological assessment and central review of non-palpable breast carcinoma specimens and sentinel nodes was observed in 24% of patients. This inter-observer variation would have impacted locoregional and/or systemic treatment strategies in 8% of the patients.

Abstract P5-08-01: Contemporary local and regional recurrence rates in very young breast cancer patients

Introduction: Historically, young breast cancer patients proved to have a poorer prognosis regarding survival and locoregional recurrence. Over the last two decades, the survival of breast cancer patients has improved substantially, while at the same time locoregional recurrence rates decreased. The diminishing recurrence rates in the overall breast cancer population and acknowledgement of tumor biology and intrinsic subtypes in relation to age, raise the question whether the historically high locoregional recurrence risk in young women has decreased over a time where systemic treatment has evolved, particularly for the aggressive tumor types that occur frequently in young women. The aim of this study was to evaluate contemporary local and regional recurrence rates in very young breast cancer patients in relation to tumor biology in the shape of intrinsic subtypes. Methods: Women Results: A total of 1,000 patients were identified. The overall 5-year LR and RR rates were 3.5% and 3.7% respectively and a decreasing trend for both rates was observed over time. Intrinsic subtype proved to be a prognostic factor for both LR and RR (P=0.0556 and P=0.0141, respectively). Particularly HR-/HER2+ tumors were associated with high LR and RR rates. Patients with lymph node metastases at time of diagnosis had a higher RR-risk in both the total population (P=0.0349) as well as within the different intrinsic subtypes, although only significantly in the triple negative group (P=0.0401). Type of surgery did not influence the rate of LR and RR in this study. Conclusions: Overall, the LR and RR rates in very young breast cancer patients were relatively low and decreased over time. The higher recurrence rates in this population were associated with the presence of more aggressive intrinsic subtypes. We emphasize that tumor biology should guide decision-making towards optimal treatment in this specific population. Although longer follow-up is needed, especially for this very young patient population, the results of this study provide important insight in the locoregional recurrence risks for this historically high-risk population. Citation Format: Aalders KC, Postma EL, Strobbe LJ, van der Heiden-van der Loo M, Sonke GS, Boersma LJ, van Diest PJ, Siesling S, van Dalen T. Contemporary local and regional recurrence rates in very young breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-01.

Abstract P5-15-03: Prediction of positive resection margins in patients with non-palpable breast cancer

Background Obtaining tumor free resection margins is essential in patients undergoing breast conserving surgery. Several risk factors associated with positive margins are described in literature. We developed a prediction model to predict positive resection margins in patients undergoing breast conserving surgery of non-palpable lesions. Methods A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery at five different hospitals in the Netherlands. A prediction model for positive resection margins was built using multivariate regression analysis and internally validated by bootstrapping. Results Positive resection margins were present in 69/576 (12%) patients. Factors associated with positive margins included microcalcifications on mammography (OR 1.8, 1.0-3.2), tumor not visible on ultrasound (OR 2.6, 1.2-5.6), presence of DCIS (OR 2.3, 1.3-4.0), multifocality (OR 3.5, 1.0-12.1), caudal location in the breast (OR 1.9, 1.1-3.5), and invasive tumor size (OR 1.83, 1.6-2.7). Together, these factors were able to moderately discriminate between patients with positive versus negative margins (area under the ROC 0.71, 95% CI 0.648 – 0.780). After internal validation the discrimination was slightly lower with an AUC of 0.694. Prevalence of positive margins was 5.2% in the highest risk quintile versus 26.3% in the lowest quintile. Conclusion A model predicting positive resection margins after breast conserving surgery in non-palpable breast cancer was built. This model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning (eg. preoperative MRI) and informing of patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-03.